Enhanced activity alcohol-based antimicrobial compositions

ABSTRACT

Antimicrobial compositions which can be used wherever disinfecting compositions are needed, such as in a hospital, healthcare industry, workplace, recreational facility, home or similar environment. The antimicrobial compositions are particularly useful as a topical application for a substrate, such as skin and can be used as a hand sanitizer or pre-surgical scrub. The compositions comprise a synergistic combination of a simple aliphatic alcohol and an activity enhancing substance, wherein the composition provides, heretofore unexpected, persistent activity against a broad range of microorganisms, including gram-negative organisms, while moisturizing the skin.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to antimicrobial compositions which can beused wherever disinfecting compositions are needed, such as in ahospital, healthcare industry, workplace, recreational facility, home orsimilar environment. The antimicrobial compositions are particularlyuseful as a topical application for a substrate, such as skin and can beused as a hand sanitizer or pre-surgical scrub. The compositionscomprise a synergistic combination of a simple aliphatic alcohol and anactivity enhancing substance, wherein the composition provides,heretofore unexpected, persistent activity against a broad range ofmicroorganisms, including gram-negative organisms, while moisturizingthe skin.

Various forms of antimicrobial compositions containing alcohols areknown in the art and have been used in the healthcare industry for sometime. The antimicrobial compositions are typically utilized to cleansethe skin and destroy bacteria and other microorganisms present thereon,especially on the hands, arms, and face of the user.

An important use of the antimicrobial composition is to disinfect thehands and fingers of a person. The composition is generally applied to,and rubbed into the hands and fingers, and subsequently allowed toevaporate from the skin. Wiping of the composition from the skin istypically not necessary because of the alcohol content of thecompositions which leads to fast and essentially complete evaporation ofthe composition from the skin.

Antimicrobial compositions in general have been used in the healthcareindustry, food service industry, meat processing industry, and in theprivate sector by individual consumers to control and prevent the spreadof potentially harmful microorganisms. The widespread use ofantibacterial compositions indicates the importance of controllingbacteria and other microorganism populations on the skin or othersubstrates. It is important, that the antimicrobial compositions reducemicroorganism populations rapidly, without irritating or damaging skinor having a detrimental toxicity. The prior art antimicrobialcompositions generally contain a high percentage of alcohol, wherein thealcohol acts as a disinfectant which rapidly evaporates preventing theneed to wipe or rinse the composition from the treated surface. However,it has been found that high amounts of alcohol generally greater thanabout 60% dry and/or irritate skin.

U.S. Pat. No. 5,288,486 relates to a process for enhancing the efficacyof alcohol-based skin antiseptics comprising adding at least onealcohol-soluble viscosifying agent to an alcohol-based disinfectant,thereby lowering its alcohol evaporation rate and markedly increasingthe exposure time that disinfecting concentrations of alcohol arepresent on skin.

U.S. Pat. No. 5,635,462 relates to a reportedly cleansing compositionincluding a substituted phenol such as para-chloro-meta-xylenol, and atleast one primary surfactant selected from the group consisting of amineoxides, phospholipids, partially neutralized carboxylic acids anddiacids, betaines, ethoxylated methyglucosides, and mixtures thereof.Other additives such as viscosifiers or thickeners, emollients,fragrances, perfumes, coloring agents, and the like may also be added.

U.S. Pat. No. 5,997,893 relates to reportedly antimicrobial compositionscontaining high levels of alcohol, carbomer polymers and antimicrobialagents which provide formulations possessing cosmetic characteristics.

U.S. Pat. No. 6,022,551 relates to reportedly antimicrobialalcohol-containing composition and method of using the composition toreportedly disinfect surfaces, such as the hands is disclosed.

U.S. Pat. No. 6,136,771 relates to reportedly antibacterial compositionshaving a reduced amount of disinfecting alcohol. The antibacterialcompositions contain a phenolic antibacterial agent, a disinfectingalcohol, a gelling agent, and water, wherein a percent saturation of theantibacterial agent in a continuous aqueous phase of the composition isat least 25%.

U.S. Pat. No. 6,228,385 relates to a liquid reportedly antimicrobial,skin moisturizing formulation including: 1) an aqueous alcoholic base;2) a humectant; 3) a delivery material adapted to release an emollientwhen the formulation is applied to the skin; and 4) an emollientimmiscible in the aqueous alcoholic base and contained by the deliverymaterial. The delivery material reportedly encapsulates or entraps theemollient for subsequent release. Desirably, the humectant is glycerinand the emollient is an alkyl-substituted polysiloxane polymer.

U.S. Pat. No. 6,423,329 relates to compositions and methods ofsanitizing and moisturizing skin surfaces.

U.S. Pat. No. 6,723,689 relates to a reportedly antimicrobialcomposition comprising an alcohol in an amount from about 60 to about 95weight percent of the total composition, a preservative, a cationiccellulose polymer thickening agent, a moisturizer and/or cationicemulsifier, and water in an amount from about 6 to about 30 weightpercent.

A need exists for antimicrobial compositions which are effective againsta broad spectrum of microorganisms including gram positive and gramnegative bacteria and provide enhanced antimicrobial activity and thusprovide a longer period of protection for the user.

SUMMARY OF THE INVENTION

Antimicrobial compositions are disclosed which provide enhanced orprolonged activity against various microorganisms. The aliphatic alcoholconcentration of the compositions is kept at a moderate level in orderto prevent irritation to skin. It has been unexpectedly found thatactivity enhancing substances synergistically combine with the aliphaticalcohol in the compositions of the present invention to provide residualactivity on a substrate and prevent subsequent microorganism growth whencompared to alcohol alone. It is believed that the compositions retardevaporation of the alcohol and/or other antimicrobial agent if present,and increasing the contact time with the substrate i.e., skin beingtreated; or bind with the skin and remain on the surface therebymaintaining effectiveness against subsequent contact with amicroorganism; or combinations thereof.

The antimicrobial compositions comprise an aliphatic alcohol, preferablyin an amount of about 50 to about 58 parts by weight, one or moreactivity enhancing substances in a range from about 0.0125 to about 10parts by weight, and water based on 100 parts by weight of theantimicrobial composition. The compositions can optionally include othercomponents including, but not limited to, humectants, skin conditioners,emollients, viscosifying agents, preservatives, and fragrances.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood and other features andadvantages will become apparent by reading the detailed description ofthe invention, taken together with the drawings, wherein:

FIG. 1 illustrates residual activity values in average log reduction ofcompositions containing various additives; and

FIG. 2 illustrates additional residual activity values in average logreduction of compositions containing various additives.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to enhanced activity alcohol-basedantimicrobial compositions which are preferably utilized as skindisinfectants or antiseptics which provide the skin or other surfacewith prolonged antimicrobial properties. Methods for preparingantimicrobial compositions are also described.

Alcohol-containing or alcohol-based antimicrobial compositions aretypically drying and even irritating to the skin, especially whenutilized repeatedly as required in the healthcare field. While searchingfor components which could increase the moisturizing capabilities of analcohol-based composition, it was unexpectedly discovered thatcompositions could be formulated comprising an aliphatic alcohol and anactivity enhancing substance, which exceeded the activity of acomposition without the latter component. In most cases, themoisturizing ability of the compositions are improved in addition toproviding increased activity of the composition against microorganisms.

The compositions of the present invention include an aliphatic alcoholwhich has inherent antiseptic properties. Such alcohols are known tokill various viruses, fungi, mold, and gram positive and gram negativebacteria. Suitable alcohols are short chain, linear or branched,aliphatic alcohols, and generally have from 1 to about 8 carbon atomswith 1 to about 4 carbon atoms being preferred. Examples include, butare not limited to, methanol, ethanol, in-propanol, isopropyl alcohol,2-methyl-2 propanol and hexanol, or combinations thereof. Propanol,isopropyl alcohol and ethanol are preferred.

The aliphatic alcohol is present in a range generally from 30 parts toabout 90 parts, desirably from about 45 parts to less than about 60parts, and preferably from about 50 parts to abut 57 or 58 parts byweight per 100 parts by weight of the composition. It has beenunexpectedly found that compositions having less than 60 parts aliphaticalcohol can be effective antimicrobials having enhanced activity.

The alcohol is combined with an activity enhancing substance whichincreases the residual activity of the composition and beneficially theeffectiveness of the antibacterial activity as indicated by a logreduction in microorganisms. Typical prior art antibacterialcompositions generally offer a low to moderate antibacterial activity.Antibacterial activity is assessed against a broad spectrum ofmicroorganisms, including both gram positive and gram negative bacteria.Log reduction or alternatively percent reduction, in bacterialpopulations provided by the composition correlates to antibacterialactivity. Log reductions on skin of between one and three are desired,and log reductions greater than three are preferred for a particularcontact time which generally ranges from 15 seconds to about 5 minutes.

The activity enhancing substance can generally be classified as one oftwo types, an aromatic alcohol activity enhancing substance, or acationic substrate binding activity enhancing substance. One orpreferably both types of activity enhancing substances are utilized inthe compositions of the present invention. Suitable cationic substratebinding activity enhancing substances include, but are not limited to,behentrimonium methosulfate, behenalkonium chloride, behenoylPG-trimonium chloride, behenoyl PG-dimonium chloride, behenamidopropylPG-dimonium chloride, or combinations thereof. The cationic substratebinding activity enhancing substances are utilized in the antimicrobialcompositions in amounts which range generally from about 0.0125 to about0.50 parts, desirably from about 0.03 to about 0.10 parts, andpreferably from about 0.04 to about 0.075 parts based on 100 parts byweight of the composition. Some of the substrate binding activityenhancing substances are commercially available as blends at variousconcentrations. Often, the substrate binding activity enhancingsubstances are blended with one or more long chain aliphatic alcoholshaving greater than about 10 carbon atoms such as, but not limited to,cetyl alcohol, stearyl alcohol, behenyl alcohol or cetearyl alcoholwhich is generally a 50/50 mixture by weight of cetyl and stearylalcohol.

The aromatic alcohol activity enhancing substances include at least onephenyl group and an alcohol functional group indirectly attached to thephenyl ring, such as through aliphatic linkage or ether linkage, forexample. Suitable aromatic alcohol activity enhancing substancesinclude, but are not limited to, phenoxyethanol, 1-phenoxy 2-propanol,and benzyl alcohol. The aromatic alcohol activity enhancing substancesare utilized in the antimicrobial compositions in amounts which rangegenerally from about 0.5 to about 5.0, desirably from about 0.75 toabout 3.5, and preferably from about 1.0 to about 2.5 parts based on 100parts by weight of the composition.

Polyols are optionally but preferably utilized in the antimicrobialcompositions of the present invention. Polyols contain from 2 to about 6and desirably 2 or 3 hydroxyl groups. Preferred polyols are watersoluble. The polyols utilized in the present invention are typicallyskin conditioners such as humectants or moisturizers. Specific examplesof polyols include, but are not limited to, ethylene glycol, propyleneglycol, glycerol, diethylene glycol, triethylene glycol, dipropyleneglycol, tripropylene glycol, hexylene glycol, butylene glycol,1,2,6-hexanetriol, sorbitol, PEG-4 and similar polyhydroxy compounds,are 2-methyl-1,3-propane diol.

In addition to the polyols, the antimicrobial compositions of thepresent invention can include other skin conditioners such ashumectants, emollients, moisturizers or the like. Emollients aregenerally thin liquids, oils of various viscosities, fatty solids orwaxes. A function of the skin conditioner is to soften and soothe theskin and to prevent chapping of the same. Preferably the skinconditioner chosen does not leave a tacky feel on the skin. Examples ofsuch compounds include, but are not limited to, cyclomethicone, cetylmyristate, glyceryl dioleate, isopropyl myristate, lanolin, methyllaurate, PPG-9 laurate, soy stearyl, octyl palmitate, Di-PPG-3 myristylether adipate, C12-C15 alkyl benzoates, PPG-5 lanoate, glucamine andpyridoxine glycol, for example. Occlusive skin conditioners, forexample, cetyl lactate, aluminum lanolate, corn oil, dimethicone,coconut oil, stearyl stearate, phenyl trimethicone, trimyristin, oliveoil, and synthetic wax, also can be used. Combinations of the classes ofskin conditioners, in addition to miscellaneous skin conditioners knownto persons skilled in the art, alone or in combination can be used.Nonlimiting examples of miscellaneous skin conditioners include aloe,cholesterol, cystine, keratin, lecithin, egg yolk, glycine, PPG-12,retinol, salicylic acid, orotic acid, vegetable oil, and soluble animalcollagen. The skin conditioners can be used alone, or in combinationwith a skin protectant, like petroleum, cocoa butter, calamine, andkaolin, for example.

Still other skin conditioners include alcohol soluble polyquaterniums,including but not limited to, Merquat 100, which isN,N-dimethyl-N-2-propen-1-aminium chloride, polyquaternium 22 (acrylicacid-diallydimethylammonium chloride polymer) and polyquaternium 47(1-propanaminium,N,N,N-trimethyl-3-((2-methyl-1-oxo-2-propenyl)amino)-chloride polymerwith methyl 2-propenoate and 2-propenoic acid), all commerciallyavailable from ONDEO Nalco of Naperville, Ill.

One or more skin conditioners, emollients, humectants, or the like canbe utilized in the antimicrobial compositions of the present inventionin total amounts which range generally from about 0.25 to about 10parts, desirably from about 0.50 to about 5.0 parts, and preferably fromabout 1.0 to about 3.5 parts based on 100 parts by weight of thecomposition.

Thickening agents are optionally but preferably utilized in theantimicrobial compositions of the present invention in order to increasethe viscosity thereof. Thickening compounds can be both organic andinorganic. The antimicrobial compositions of the present invention canbe a liquid but typically contain a sufficient amount of a thickeningagent such that the composition is a viscous liquid or flowable gel thatcan be easily applied to a substrate such as skin. The type and amountof thickeners utilized in the composition depend upon the desiredviscosity thereof among other factors. That said, a thickener, whenutilized in the present invention, is present in a range generally fromabout 0.1 to about 3.0 parts, desirably from about 0.15 to about 1.0part, and preferably from about 0.2 to about 0.75 parts based on 100parts by weight of the composition.

The compositions of the present invention have viscosities which rangegenerally from about 10 to 100,000 centipoise(cp), desirably from about30 to about 5,000 centipoise(cp), and preferably from about 60 to about120 centipoise (cp) as measured using a low shear viscositydetermination method such as the helipath method using an inverted “t”spindle as known in the art (Brookfield Method).

Various thickeners can be utilized to thicken the aqueous and/ornon-aqueous portion of the antimicrobial composition. Examples ofsuitable thickeners include, but are not limited to, acacia,acrylates/steareth-20 methacrylate copolymer, agar, algin, alginic acid,ammonium acrylate copolymers, ammonium alginate, ammonium chloride,ammonium sulfate, amylopectin, attapulgite, bentonite, C9-15 alcohols,calcium acetate, calcium alginate, calcium carrageenan, calciumchloride, caprylic alcohol, carbomer 910, carbomer 934, carbomer 934P,carbomer 940, carbomer 941, carboxymethyl hydroxyethylcellulose,carboxymethyl hydroxypropyl guar, carrageenan cellulose, cellulose gum,cetearyl alcohol, cetyl alcohol, corn starch, damar, dextrin,dibenzylidine sorbitol, ethylene dihydrogenated tallowamide, ethylenedioleamide, ethylene distearamide, gelatin, guar gum, is guarhydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydratedsilica, hydroxybutyl methylcellulose, hydroxyethylcellulose,hydroxyethyl ethylcellulose, hydroxyethyl stearamide-MIPA,hydroxypropylcellulose, 2-hydroxypropyl ether cellulose, hydroxypropylguar, hydroxypropyl methylcellulose, isocetyl alcohol, isostearylalcohol, karaya gum, kelp, lauryl alcohol, locust bean gum, magnesiumaluminum silicate, magnesium silicate, magnesium trisilicate, methoxyPEG-22/dodecyl glycol copolymer, methylcellulose, microcrystallinccellulose, montmorillonite, myristyl alcohol, oat flour, oleyl alcohol,palm kernel alcohol, pectin, PEG-2M, PEG-5M, polyacrylic acid, polyvinylalcohol, potassium alginate, potassium aluminum polyacrylate, potassiumcarrageenan, potassium chloride, potassium sulfate, potato starch,propylene glycol alginate, sodium acrylate/vinyl alcohol copolymer,sodium carboxymethyl dextran, sodium carrageenan, sodium cellulosesulfate, sodium chloride, sodium polymethacrylate, sodiumsilicoaluminate, sodium sulfate, stearalkonium bentonite, stearalkoniumhectorite, stearyl alcohol, tallow alcohol, TEA-hydrochloride,tragacanth gum, tridecyl alcohol, tromethamine magnesium aluminumsilicate, wheat flour, wheat starch, xanthan gum, and mixtures thereof.

The following additional nonlimiting examples of thickening agents actprimarily by thickening the nonaqueous portion of the composition:abietyl alcohol, acrylinoleic acid, aluminum behenate, aluminumcaprylate, aluminum dillinoleate, aluminum distearate, aluminumisostearates/laurates/palmitates or stearates, aluminumisostearates/myristates, aluminum isostearates/palmitates, aluminumisostearates/stearates, aluminum lanolate, aluminummyristates/palmitates, aluminum stearate, aluminum stearates, aluminumtristearate, beeswax, behenamide, behenyl alcohol,butadiene/acrylonitrile copolymer, C29-70 acid, calcium behenate,calcium stearate, candellilia wax, carnauba, ceresin, cholesterol,cholesteryl hydroxystearate, coconut alcohol, copal, diglyceryl stearatemalate, dihydroabietyl alcohol, dimethyl lauramine oleate, dodecanedioicacid/cetearyl alcohol/glycol copolymer, erucamide, ethylcellulose,glyceryl triacetyl hydroxystearate, glyceryl tri-acetyl ricinoleate,glycol dibehenate, glycol di-octanoate, glycol distearate, hexanedioldistearate, hydrogenated C8-14 olefin polymers, hydrogenated castor oil,hydrogenated cottonseed oil, hydrogenated lard, hydrogenated menhadenoil, hydrogenated palm kernel glycerides, hydrogenated palm kernel oil,hydrogenated palm oil, hydrogenated polyisobutene, hydrogenated soybeanoil, hydrogenated tallow amide, hydrogenated tallow glyceride,hydrogenated vegetable glyceride, hydrogenated vegetable glycerides,hydrogenated vegetable oil, hydroxypropyl-cellulose,isobutylene/isoprene copolymer, isocetyl stearcyl stearate, Japan wax,jojoba wax, lanolin alcohol, lauramide, methyl dehydroabietate, methylhydrogenated rosinate, methyl rosinate, methylstyrene/vinyltoluenecopolymer, microcrystalline wax, montan acid wax, montan wax,myristyleicosanol, myristyloctadecanol, octadecene/maleic anhydridecopolymer, octyldodecyl stearoyl stearate, oleamide, oleostearine,ouricury wax, oxidized polyethylene, ozokerite, palm kernel alcohol,paraffin, pentaerythrityl hydrogenated rosinate, pentaerythritylrosinate, pentaerythrityl tetraabietate, pentaerythrityl tetrabehenate,pentaerythrityl tetraoctanoate, pentaerythrityl tetraoleate,pentaerythrityl tetrastearate, phthalic anhydride/glycerin/glycidyldecanoate copolymer, phthalic/trimellitic/glycols copolymer, polybutene,polybutylene terephthalate, polydipentene, polyethylene, polyisobutene,polyisoprene, polyvinyl butyral, polyvinyl laurate, propylene glycoldicaprylate, propylene glycol dicocoate, propylene glycoldiisononanoate, propylene glycol dilaurate, propylene glycoldipelargonate, propylene glycol distearate, propylene glycoldiundecanoate, PVP/elcosene copolymer, PVP/hexadecene copolymer, ricebran wax, stearalkonium bentonite, stearalkonium hectorite, stearamide,stearamide DEA-distearate, stearamide DIBA-stearate, stearamideMEA-stearate, stearone, stearyl alcohol, stearyl erucamide, stearylstearate, stearyl stearoyl stearate, synthetic beeswax, synthetic wax,trihydroxystearin, triisononanoin, triisostearin, triisononanoin,triisostearin, tri-isostearyl trilinoleate, trilaurin, trilinoleic acid,trilinolein, trimyristin, triolein, tripalmitin, tristearin, zinclaurate, zinc myristate zinc neodecanoate, zinc rosinate, zinc stearate,and mixtures thereof.

In a preferred embodiment, the thickener utilized is a non-ionicthickener such as 2-hydroxypropyl ether cellulose available from Aqualonas Klucel HF. The compositions of the present invention are preferablyfree of both anionic and cationic thickening agents. The use ofnon-ionic thickeners provides broad compatibility with the wide range offormulation ingredients utilized. Antipodally, anionic or cationicthickeners can inactivate antimicrobial agents utilized in thecompositions of the invention.

The antimicrobial compositions of the present invention utilize water,preferably deionized water, as a carrier. Water is utilized in a rangegenerally from about 5 or 20 to about 65 parts, desirably from about 33or 35 to about 50 parts, and preferably from about 37 to about 45 partsbased on 100 parts by weight of the composition.

The compositions of the present invention optionally include apreservative component. Examples of suitable preservatives include, butare not limited to, chlorhexidine gluconate, chlorhexidine acetate,chlorhexidine isethionate, chloroxylenol, triclosan, methyl paraben,propyl paraben, butyl paraben, quaternium 15, DMDM hydantoin,iodopropynybutyl carbamate, diazolindinyl urea, imidazolidinyl urea,parachlormetaxylenol, chlorhexidine diacetate, glyceryl monolaurate,pyrithione (zinc, sodium, and MDS), 2-bromo-2-nitropropane-1,3-diol,chloroacetamide, triclocarban, propamidine, isethionate, hexamidineisetnionate, hexetidine, polyhexamethylene biguanide hydrochloride,alkyltrimethylammonium, bromide, benzalkonium, chloride and benzethoniumchloride. The preservative is utilized in the present invention invarious amounts.

The antimicrobial compositions of the present invention can containoptional ingredients which include, but are not limited to, dyes,fragrances, pH adjusters, buffering agents, antioxidants, emulsifiersand surfactants. The optional ingredients can be utilized in variousamounts to achieve a desired effect on the composition, as known tothose of ordinary skill in the art. Examples of suitable dyes include,but are not limited to, D&C blue 1, D&C brown 1, D&C green 5, D&C green6, D&C green 8, D&C orange 4, D&C orange 5, D&C orange11, D&C orange 12,D&C red 6, D&C red 7, D&C red 17, D&C red 21 D&C red 27, D&C red 30, D&Cred 33 D&C red 34, D&C red 36, D&C violet 2, D&C yellow 10, D&C yellow11, D&C yellow 7, D&C yellow 8, FD&C blue 1, FD&C green 3, FD&C red 4,FD&C red 40, FD&C yellow 5, FD&C yellow 6, or any blend thereof.

The pH adjusters can be utilized if desired in order to impart thecompositions of the present invention with a pH of about 4 to about 8,and preferably from about 4.5 to about 5, if the composition is notalready within the noted ranges. The pH adjusters include, but are notlimited to, ammonia, sodium hydroxide, potassium hydroxide, lithiumhydroxide, ethanol amine, triethyl amine, isopropanol amine,diisopropanol amine, tromethamine, tetrahydroxy propyl ethylene diamine,isopropyl amine, diethanol amine, triethyanol amine, citric acid,glycolic acid, lactic acid, hydrochloric acid, nitric acid, phosphoricacid, salicylic acid, and sulfuric acid.

In some embodiments, additional antimicrobial compounds can be utilizedin the compositions of the present invention. Suitable antimicrobialsinclude, but are not limited to, benzalkonium chloride, benzethoniumchloride, CHG or phenols, optionally substituted, such as triclosan,some of which as noted above, also have other functions such as being apreservative. In most embodiments however, the compositions of thepresent invention are free of such antimicrobials other than thealiphatic alcohol and activity enhancing substances.

The present invention will be better understood by reference to thefollowing examples which serve to describe, but not to limit, thepresent invention.

EXAMPLES

Various compounds were tested in the aliphatic alcohol-based formulationset forth in Table I to determine if moisturization could be improved.It was unexpectedly discovered during experimentation that one of thecomponents utilized, behentrimonium methosulfate enhanced activity ofthe alcohol composition against Serratia Marcescens ATCC 14756.Following this unexpected discovery, various other compounds, includingquaternary ammonium compounds, were tested in the formulation of Table Ito determine if any enhanced activity could also be observed. Testingshowed that very few quaternary ammonium compounds offered substantialenhanced activity, whereas a majority of quaternary ammonium compoundsshow little or even a negative effect on antimicrobial activity.

TABLE I Component Weight Percent Deionized Water 40.990 Polyquaternum 60.480 Cetyl lactate 0.480 Hydroxypropyl cellulose 0.240 Fragrance 0.024Isopropyl alcohol 53.850 Methylpropanediol 1.92 Glycerin 1.92 C₁₂-C₁₅alkyl benzoate (Finsolv TN) 0.096 Total 100

Each component listed in Table II was separately added to the abovealcohol-based formulation listed in Table I and tested to determine ifantimicrobial activity could be enhanced. The weight percentages listedin Table II are based on 100 total parts by weight of the composition inTable I and the listed component. For example with Experiment A, 5 partsof phenoxyethanol was tested in 95 parts of the composition listed inTable I.

TABLE II Experiment Additive Components Weight % A Phenoxyethanol(ethylene glycol phenyl 5 ether) (90%) B Glyceryl monolaurate(Lauricidin) 1 C Methyl paraben 0.2 D Propyl paraben 0.1 E Iodopropynylbutylcarbamate 0.15 F Glydant plus (DMDM Hydantoin/IPBC) 0.08 G PCMX0.125 H Benzethonium chloride 0.13 I Triclosan 0.10 J Polyquaternium 6(40%) 0.50 K Cocoamidopropyl PG dimonium 2.0 chloride (40%) LBehentrimonium methosulfate in cetearyl 0.50 alcohol at 25% concentrate

The following procedure was utilized to prepare the example formulation.The appropriate amount of water was heated to a temperature sufficientto dissolve any solid components, such as from about 70° C. to about 80°C. for behentrimonium methosulfate. The solid components such asbehentrimonium methyosulfate were added to the water with mixingutilizing an impeller mixer. The solution was subsequently coded to atemperature of about 60° wherein hydroxypropyl cellulose was added withmixing. The solution was further cooled to allow the polymer to hydrate.The cetyl lactate, polyquaternium-6, glycerin, methylpropanediol,phenoxyethanol (in the case of experiment A) or other noted additive inTable II, and fragrance were added, preferably sequentially with mixingappropriate to disperse the materials. If necessary, additional waterwas added to replace water lost during processing as determined byappropriate vessel gross and net weights. Next, the appropriatealiphatic alcohol, such as isopropanol, was added with mixing tocomplete the composition. It is to be understood that variations of theabove-described process can be utilized. For example, multi-tankprocesses can be utilized, and/or various types of dispersing equipmentcan replace the higher temperature dispersion of some components, etc.

Residual Activity Testing Procedure

Each formulation was tested on pigskin to evaluate the effect of thecompositions on a gram negative organism. Serratia marcescens ATCC14756. The gram negative organism was grown for approximately 24 hoursat 30° C. and then suspended in Butterfields Buffer to a count of 1×10⁸.The pigskins were prepared according to the following standard ofprocedure. Pigskin hides are collected on the date of slaughter andprocessed on the same day by removing adipose tissue and thoroughlycleaning the hide. Both of these processes are accomplished by sprayingboth sides of the pig hide with a high pressure washer. No soap ordetergents are used at any time during the processing of pig hides forlaboratory use. After cleaning and de-fatting, pigskins are placed inwater and frozen at the farm from which they were harvested. Whenrequired for laboratory testing, a representative procures the hides andthaws them for laboratory manipulation. In the laboratory, these hidesare cut into manageable pieces with a scalpel and coarse hair removedwith animal grooming clippers. Disposable razors are further employed tocreate a smooth surface without negatively affecting the skin surface.These pieces are then sterilized by Gamma irradiation and kept frozenuntil use in a study. Testing circles were then punched out of thepigskins and glued to a phenolic cap. The testing samples were placed ina 30° C. oven to equilibrate for at least 20 minutes. Each skin wastreated with 150 μl of test product and rubbed for 30 seconds as a pair,skin to skin. The skins were allowed to dry for 30 seconds and then thetest product was reapplied four times in the same manner. The skins wereallowed to dry in a slightly opened hood for 15 minutes. After dryingthe skins were inoculated with 31 μl of the Serratia marcescensinoculum, as prepared above, rubbed for 15 seconds, and sampled afterthree minutes. To sample, a sterile 3.5 cm diameter cylinder is placed,lip side down, over the pigskin on the cap. Enough pressure is appliedto the cylinder to prevent any leakage upon the addition of anappropriate volume of liquid sampling solution to the cylinder. The skinis then debrided, using a sterile policeman, for 30 seconds by rubbingthe surface of the skin with the flat edge of the policeman with enoughpressure to remove any microorganisms that might be on the surface. TwomL of the sampling solution are removed using a sterile pipet and areutilized for preparing serial dilutions and aerobic plate counts toestablish the number of Colony Forming Units remaining.

FIG. 1 illustrates in average log reduction residual activity results ofthe testing procedure described above. The quaternary ammonium compoundbehentrimonium methosulfate and phenoxyethanol exhibited enhancedantimicrobial activity when compared to the remaining components listedin Table II.

FIG. 1 was derived from the following data which was gathered utilizingthe above described residual activity testing procedure.

TABLE III Average Log Log Average Series Test Product (active %)Reduction Reduction Series 1 Phenoxyethanol (5%) 3.93 3.06 3.39 2Phenoxyethanol 2.19 3 Phenoxyethanol 4.13 3.72 4 Phenoxyethanol 3.30 5Glyceryl monolaurate (1%) −0.29 −0.23 −0.21 6 Glyceryl monolaurate −0.177 Glyceryl monolaurate −0.10 −0.18 8 Glyceryl monolaurate −0.26 9 Methylparaben (0.2%) −0.16 −0.11 0.03 10 Methyl paraben −0.06 11 Methylparaben 0.16 0.17 12 Methyl paraben 0.18 13 Propyl paraben (0.1%) 1.380.85 0.40 14 Propyl paraben 0.33 15 Propyl paraben 0.01 −0.05 16 Propylparaben −0.12 17 IPBC (0.015%) −0.22 −0.15 −0.10 18 IPBC −0.07 19 IPBC−0.02 −0.05 20 IPBC −0.08 21 DMDM Hydantoin/IPBC 0.01 0.00 −0.10 (0.08%)22 DMDM Hydantoin/IPBC −0.02 23 DMDM Hydantoin/IPBC −0.11 −0.21 24 DMDMHydantoin/IPBC −0.30 25 PCMX (0.125%) 0.18 0.06 0.16 26 PCMX −0.07 27PCMX 0.26 0.26 28 PCMX 0.26 29 Benzethonium Chloride 0.03 0.51 0.17(0.13%) 30 Benzethonium Chloride 0.98 31 Benzethonium Chloride −0.32−0.17 32 Benzethonium Chloride −0.01 33 Triclosan (0.1%) −0.22 −0.23−0.04 34 Triclosan −0.24 35 Triclosan 0.13 0.15 36 Triclosan 0.18 37Polyquaternium 6 (0.2%) 0.05 0.04 0.05 38 Polyquaternium 6 0.04 39Polyquaternium 6 0.17 0.07 40 Polyquaternium 6 −0.03 41 CocoamidopropylPG −0.06 −0.13 −0.04 dimonium chloride (0.8%) 42 Cocoamidopropyl PG−0.21 dimonium chloride 43 Cocoamidopropyl PG −0.10 0.04 dimoniumchloride 44 Cocoamidopropyl PG 0.19 dimonium chloride 45 Behentrimoniummethosulfate 5.83 4.94 5.39 (0.125%) 46 Behentrimonium methosulfate 4.0547 Behentrimonium methosulfate 5.83 5.83 48 Behentrimonium methosulfate5.83

After it was unexpectedly discovered that the quaternary ammoniumcompound behentrimonium methosulfate provided increased antimicrobialactivity in the base formulation, additional quaternary ammoniumcompounds were screened to determine their effectiveness, if any. Thesame formulation utilized in Table I was utilized as the baseformulation for testing purposes. The various quaternary ammoniumcompounds listed in Table V were added to the base formulation at a rateof 0.5 parts by weight per 100 parts total composition. The baseformulation and formulations including each quaternary ammonium compoundwere tested utilizing the residual activity test procedure describedhereinabove. The results of the experiments are also listed in FIG. 2and in Table V.

TABLE IV Additive Component Weight % Phenoxyethanol 0.5 BehentrimoniumMethosulfate in cetearyl alcohol at 25% 0.5 concentration Quaternium 260.5 Babbassuamidopropalkonium Chloride 0.5 Centrimonium Chloride 0.5Hydroxyethyl behenamidopropyldimonium chloride 0.5Dioleylamidoethylmonium methosulfate, propylene glycol 0.5Isostearyamidopropyl morpholine lactate 0.5 Olealkonium Chloride 0.5Stearamidopropyl dimethylamine lactate 0.5 Cinnamidopropyltrimethylammonium chloride 0.5 Stearalkonium chloride 0.5 BehenalkoniumChloride 0.5 Glyceryl caprate 0.5 Sodium Coco PG-Dimonium chloridephosphate 0.5

TABLE V Average Log Log Log Series Test Product Value ReductionReduction 1 Base 6.28 −0.18 −0.27 2 Base 6.46 −0.36 3 Phenoxyethanol1.00 5.10 5.60 4 Phenoxyethanol 0.00 6.10 5 Behentrimonium methosulfate0.00 6.10 5.25 6 Behentrimonium methosulfate 1.70 4.40 7 Quaternium 266.20 −0.11 −0.07 8 Quaternium 26 6.13 −0.03 9 Babbassuamidopropalkonium5.82 0.28 0.35 chloride 10 Babbassuamidopropalkonium 5.68 0.42 chloride11 Cetrimonium chloride 4.87 1.23 1.24 12 Cetrimonium chloride 4.85 1.2513 Hydroxyethyl 5.19 0.91 0.63 behenamidopropyldimonium chloride 14Hydroxyethyl 5.75 0.35 behenamidopropyldimonium chloride 15 IPEG-3 5.840.26 0.27 Dioleylamidoethylmonium methosulfate 16 IPEG-3 5.81 0.29 17Isostearyamidopropyl 6.17 −0.07 −0.09 morpholine lactate 18Isostearyamidopropyl 6.20 −0.10 morpholine lactate 19 Olealkoniumchloride 5.76 0.34 0.31 20 Olealkonium chloride 5.81 0.29 21Stearamidopropyl 6.22 −0.12 −0.04 dimethylamine lactate 22Stearamidopropyl 6.05 0.05 dimethylamine lactate 23 Cinnamidopropyl 5.980.12 0.05 trimethylammonium chloride 24 Cinnamidopropyl 6.12 −0.02trimethylammonium chloride 25 Stearalkonium chloride 5.93 0.17 0.25 26Stearalkonium chloride 5.77 0.33 27 Behenalkonium chloride 1.60 4.504.41 28 Behenalkonium chloride 1.78 4.32 29 Behentrimonium chloride 5.780.32 0.33 30 Behentrimonium chloride 5.76 0.34 31 Glyceryl caprate 5.170.93 0.92 32 Glyceryl caprate 5.19 0.91 33 Sodium Coco PG-Dimonium 5.690.41 0.40 chloride phosphate 34 Sodium Coco PG-Dimonium 5.71 0.39chloride phosphate

As illustrated in the above Table V, the quaternary ammonium compoundsbehentrimonium methosulfate and behenalkonium chloride containingcompositions exhibited excellent log reduction values and antimicrobialactivity against the microbe Serratia Marcescens. The other quaternaryammonium compound containing compositions tested exhibited little or noantimicrobial activity. As evident from the table, the activity isunexpected.

In accordance with the patient statutes, the best mode and preferredembodiment have been set forth, the scope of the invention is notlimited thereto, but rather by the scope of the attached claims.

1. A composition having antimicrobial properties, comprising: analiphatic alcohol having from 1 to about 8 carbon atoms in an amountfrom about 30 to less than 60 parts; an aromatic alcohol in an amountfrom about 0.5 to about 5.0 parts, wherein the hydroxyl group of thearomatic alcohol is connected to a non-aromatic ring carbon atom; acationic substrate binding activity enhancing substance in an amountfrom about 0.0125 to about 0.5 part, wherein the cationic substratebinding activity enhancing substance is behentrimonium methosulfate orbehenalkonium chloride or a combination thereof; and water in an amountfrom about 33 to about 65 parts, all said parts based on 100 parts byweight of the composition, said composition free of a cationic cellulosepolymer.
 2. The composition according to claim 1, wherein the aliphaticalcohol is present in an amount from about 45 to less than 60 parts, andwherein the aromatic alcohol is present in an amount from 0.75 to about3.5 parts.
 3. The composition according to claim 2, wherein the water ispresent in an amount from about 33 to about 50 parts, and wherein thecationic substrate binding activity enhancing substance is present in anamount from 0.03 to about 0.1 part.
 4. The composition according toclaim 3, wherein the composition further includes a non-ionic thickener.5. The composition according to claim 2, wherein the composition has aviscosity of from about 10 to about 100,000 centipoise, and wherein saidaliphatic alcohol is methanol, ethanol, n-propanol, isopropyl alcohol,2-methyl-2 propanol, hexanol, or combinations thereof.
 6. Thecomposition according to claim 5, wherein said aliphatic alcohol ispresent in an amount from about 50 to about 55 parts, and wherein saidaromatic alcohol is present in an amount from about 1.0 to about 2.5parts, and wherein said cationic substrate binding activity enhancingsubstance is present in an amount from about 0.04 to about 0.075 parts.7. The composition according to claim 6, wherein the aliphatic alcoholis propanol, isopropyl alcohol, or ethanol, or combinations thereof, andwherein said aromatic alcohol is phenoxyethanol, benzyl alcohol,1-phenoxy-2-propanol, or combinations thereof.
 8. The compositionaccording to claim 4, wherein the non-ionic thickener is acellulose-based thickener in an amount from about 0.1 to about 3.0parts.
 9. The composition according to claim 8, wherein the compositionfurther includes a polyol, a skin conditioner, or pH adjusters orcombinations thereof.
 10. The composition according to claim 9, whereinthe viscosity of the composition is 30 to about 120 centipoise, whereinthe thickener comprises 2-hydroxypropyl cellulose, and wherein water ispresent in an amount from about 35 to about 45 parts.
 11. A method forforming an antimicrobial composition, comprising the steps of: providingfrom 33 to about 65 parts of water to a vessel; adding a cationicsubstrate binding activity enhancing substance to the vessel in anamount from about 0.0125 to about 0.5 part, wherein the cationicsubstrate binding activity enhancing substance is behentrimoniummethosulfate or behenalkonium chloride or a combination thereof; addingan aromatic alcohol to the vessel in an amount from about 0.5 to about5.0 parts, wherein the hydroxyl group of the aromatic alcohol isconnected to a non-aromatic ring carbon atom; adding an aliphaticalcohol having from 1 to about 8 carbon atoms to the vessel in an amountfrom about 30 to about 58 parts; adding a non-ionic thickener to thevessel; and mixing the composition in the vessel, wherein the parts arebased on 100 parts by weight of the composition, and wherein thecomposition is free of a cationic thickener.
 12. The method according toclaim 11, wherein the composition has a viscosity of from about 10 toabout 100,000 centipoise, and wherein said aliphatic alcohol ismethanol, ethanol, n-propanol, isopropyl alcohol, 2-methyl-2 propanol,hexanol, or combinations thereof.
 13. The method according to claim 12,wherein the cationic substrate binding activity enhancing substance ispresent in an amount from about 0.03 to about 0.1 part, wherein saidaromatic alcohol is present in an amount from about 0.75 to about 3.5parts, and wherein the aliphatic alcohol is present in an amount fromabout 45 to about 58 parts.
 14. The method according to claim 13,wherein the water is present in an amount from about 35 to about 50parts.
 15. The method according to claim 14 wherein the nonionicthickener is a cellulose-based thickener in an amount from about 0.1 toabout 3.0 parts, and wherein the composition further includes a polyol,a skin conditioner, pH adjusters or combinations thereof.